title: [Effects of immature dendritic cells to express CCR7 on graft-versus-host disease in allogeneic bone marrow transplant mouse model].
abstract: OBJECTIVE
  To investigate the effects of immature dendritic cells (imDC) expressing chemokine receptor-7 (CCR7) on acute graft-versus-host disease (aGVHD) in allogeneic bone marrow transposed (allo-BMT) mouse model.
  
  
  METHODS
  We constructed the lentiviral vectors carrying mouse CCR7 gene and infect imDC effectively in vitro. GVHD model was established with C57BL/6(H-2b) donor mice and BALB/c (H-2d) recipient mice. After irradiation, recipients were injected with donor bone marrow and spleen cells along with CCR7-modified dendritic cells. Mice were randomized into irradiation, transplant control, pXZ9-imDC (empty vector control) and CCR7-imDC groups. Survival, GVHD score, histopathological analysis and plasma levels of inflammatory cytokines were observed.
  
  
  RESULTS
  The mean survival in irradiation, transplantation, pXZ9-imDC and CCR7-imDC groups were (8.20±1.48)d, (12.20±2.78)d, (20.70±6.01)d and (27.5±7.55)d respectively. The survival in CCR7- imDC group was significantly improved compared with other groups (P<0.05). GVHD scores in transplantation, pXZ9-imDC and CCR7-imDC groups were (6.90±1.66), (5.60±0.97) and (4.10±1.79) respectively. CCR7-imDC group had significantly lower GVHD score and minor tissue damages shown by histopathological analysis than the other groups. Plasma IFN-γ level increased and reached the peak at +10 day in transplant group, while it gradually decreased in pXZ9-imDC and CCR7-imDC groups, and then reached the nadir at +20 day post-allo-BMT, with the lowest level in CCR7-imDC group (P<0.01). Plasma IL-4 decreased in transplant group, while it gradually increased in pXZ9-imDC and CCR7-imDC groups and reached the highest level at + 10 day in CCR7- imDC group (P<0.01). The 95%-100% of H-2b positive cells in recipient mice on + 30 day post-allo-BMT demonstrated the complete donor- type implantation.
  
  
  CONCLUSIONS
  Genetically modified immature DC by CCR7 gene could alleviate damages by GVHD and prolong survival of recipient mice after allo-BMT.
authors.affiliation: Department of Hematology, the Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002, China.
authors.forename: De-peng
authors.initials: DP
authors.lastname: Li
authors.forename: Jia-qing
authors.initials: JQ
authors.lastname: Wu
authors.forename: Yi-hong
authors.initials: YH
authors.lastname: Huang
authors.forename: Li-xiao
authors.initials: LX
authors.lastname: Song
authors.forename: Hong-hong
authors.initials: HH
authors.lastname: Gu
authors.forename: Cai-ling
authors.initials: CL
authors.lastname: Gao
authors.forename: Zhen-yu
authors.initials: ZY
authors.lastname: Li
authors.forename: Xiu-ying
authors.initials: XY
authors.lastname: Pan
authors.forename: Kai-lin
authors.initials: KL
authors.lastname: Xu
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation / Q000009:adverse effects; D003713:Dendritic Cells / Q000166:cytology*; D005822:Genetic Vectors; D006086:Graft vs Host Disease / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D054400:Receptors, CCR7 / Q000235:genetics*; D014184:Transplantation, Homologous
chemical_list: C515371:Ccr7 protein, mouse; D054400:Receptors, CCR7